| 1. |
|
|
| 2. |
|
|
| 3. |
- Emile-Geay, J., et al.
(författare)
-
Data Descriptor: A global multiproxy database for temperature reconstructions of the Common Era
- 2017
-
Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- Reproducible climate reconstructions of the Common Era (1 CE to present) are key to placing industrial-era warming into the context of natural climatic variability. Here we present a community-sourced database of temperature-sensitive proxy records from the PAGES2k initiative. The database gathers 692 records from 648 locations, including all continental regions and major ocean basins. The records are from trees, ice, sediment, corals, speleothems, documentary evidence, and other archives. They range in length from 50 to 2000 years, with a median of 547 years, while temporal resolution ranges from biweekly to centennial. Nearly half of the proxy time series are significantly correlated with HadCRUT4.2 surface temperature over the period 1850-2014. Global temperature composites show a remarkable degree of coherence between high-and low-resolution archives, with broadly similar patterns across archive types, terrestrial versus marine locations, and screening criteria. The database is suited to investigations of global and regional temperature variability over the Common Era, and is shared in the Linked Paleo Data (LiPD) format, including serializations in Matlab, R and Python. Since the pioneering work of D'Arrigo and Jacoby1-3, as well as Mann et al. 4,5, temperature reconstructions of the Common Era have become a key component of climate assessments6-9. Such reconstructions depend strongly on the composition of the underlying network of climate proxies10, and it is therefore critical for the climate community to have access to a community-vetted, quality-controlled database of temperature-sensitive records stored in a self-describing format. The Past Global Changes (PAGES) 2k consortium, a self-organized, international group of experts, recently assembled such a database, and used it to reconstruct surface temperature over continental-scale regions11 (hereafter, ` PAGES2k-2013'). This data descriptor presents version 2.0.0 of the PAGES2k proxy temperature database (Data Citation 1). It augments the PAGES2k-2013 collection of terrestrial records with marine records assembled by the Ocean2k working group at centennial12 and annual13 time scales. In addition to these previously published data compilations, this version includes substantially more records, extensive new metadata, and validation. Furthermore, the selection criteria for records included in this version are applied more uniformly and transparently across regions, resulting in a more cohesive data product. This data descriptor describes the contents of the database, the criteria for inclusion, and quantifies the relation of each record with instrumental temperature. In addition, the paleotemperature time series are summarized as composites to highlight the most salient decadal-to centennial-scale behaviour of the dataset and check mutual consistency between paleoclimate archives. We provide extensive Matlab code to probe the database-processing, filtering and aggregating it in various ways to investigate temperature variability over the Common Era. The unique approach to data stewardship and code-sharing employed here is designed to enable an unprecedented scale of investigation of the temperature history of the Common Era, by the scientific community and citizen-scientists alike.
|
|
| 4. |
|
|
| 5. |
- Tulstrup, M., et al.
(författare)
-
NT5C2 germline variants alter thiopurine metabolism and are associated with acquired NT5C2 relapse mutations in childhood acute lymphoblastic leukaemia
- 2018
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 32:12, s. 2527-2535
-
Tidskriftsartikel (refereegranskat)abstract
- The antileukaemic drug 6-mercaptopurine is converted into thioguanine nucleotides (TGN) and incorporated into DNA (DNA-TG), the active end metabolite. In a series of genome-wide association studies, we analysed time-weighted means ((wm)) of erythrocyte concentrations of TGN (Ery-TGN) and DNA-TG in 1009 patients undergoing maintenance therapy for acute lymphoblastic leukaemia (ALL). In discovery analyses (454 patients), the propensity for DNA-TG incorporation ((wm)DNA-TG/(wm)Ery-TGN ratio) was significantly associated with three intronic SNPs in NT5C2 (top hit: rs72846714; P - 2.09 x 10(-10), minor allele frequency 15%). In validation analyses (555 patients), this association remained significant during both early and late maintenance therapy (P - 8.4 x 10(-6) and 1.3 x 10(-3), respectively). The association was mostly driven by differences in (wm)Ery-TGN, but in regression analyses adjusted for wmEry-TGN (P < 0.0001), rs72846714-A genotype was also associated with a higher (wm)DNA-TG (P - 0.029). Targeted sequencing of NT5C2 did not identify any missense variants associated with rs72846714 or (wm)Ery-TGN/(wm)DNA-TG. rs72846714 was not associated with relapse risk, but in a separate cohort of 180 children with relapsed ALL, rs72846714-A genotype was associated with increased occurrence of relapse-specific NT5C2 gain-of-function mutations that reduce cytosol TGN levels (P = 0.03). These observations highlight the impact of both germline and acquired mutations in drug metabolism and disease trajectory.
|
|
| 6. |
- Corre, Y., et al.
(författare)
-
Testing of ITER-grade plasma facing units in the WEST tokamak: Progress in understanding heat loading and damage mechanisms
- 2023
-
Ingår i: Nuclear Materials and Energy. - : Elsevier BV. - 2352-1791. ; 37
-
Tidskriftsartikel (refereegranskat)abstract
- Assessing the performance of the ITER design for the tungsten (W) divertor Plasma Facing Units (PFUs) in a tokamak environment is a high priority issue to ensure efficient plasma operation. This paper reviews the most recent results derived from experiments and post-mortem analysis of the ITER-grade PFUs exposed in the WEST tokamak and the associated modelling, with a focus on understanding heat loading and damage evolution. Several shaping options, sharp or chamfered leading edge (LE), unshaped or shaped blocks with a toroidal bevel as foreseen in ITER, were investigated, under steady state heat fluxes of up to 120 MW⋅m−2 and 6 MW⋅m−2 on the sharp LE and top surface of the block, respectively. A very high spatial resolution (VHR) infrared (IR) camera (0.1 mm/pixel) was used to derive the temporal and surface distribution of the temperature and heat load on the castellated tungsten blocks for different geometric alignment and plasma conditions. Photonic modelling was required to reproduce the IR measurements in particular in the toroidal and poloidal gaps of the mono-block (MB) stacks where high apparent temperatures are observed. Specular reflection is found to be the dominant emitter in these parts of the blocks. W-cracking was observed on the leading edge of the blocks already within the first phase of plasma operation, during which the divertor was equipped with unshaped PFUs, including some intentionally misaligned blocks. Numerical analysis taking into account softening processes and mechanical stresses, revealed brittle failure due to transients as the dominant failure mechanisms. Ductile failure was observed in one particular block used for the melting experiment, therefore under extremely high steady state heat load conditions. W-melting achieved on actively cooled PFU exhibits specific features: shallow melting and slow melt displacement. Plasma exposure of pre-damaged PFUs at various damage levels (crack network and melted droplets) was carried out under high heat load conditions with several hours of cumulated plasma duration. IR data and preliminary surface analyses show no evidence of significant degradation damage progression under these conditions.
|
|
| 7. |
- Tulstrup, M., et al.
(författare)
-
Effects of germ line DHFR and FPGS variants on methotrexate metabolism and relapse of leukemia
- 2020
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 136:10, s. 1161-1168
-
Tidskriftsartikel (refereegranskat)abstract
- Methotrexate (MTX) during maintenance therapy is essential for curing acute lymphoblastic leukemia (ALL), but dosing strategies aiming at adequate treatment intensity are challenged by interindividual differences in drug disposition. To evaluate genetic factors associated with MTX metabolism, we performed a genome-wide association study in 447 ALL cases from the Nordic Society for Pediatric Haematology and Oncology ALL2008 study, validating results in an independent set of 196 patients. The intergenic single-nucleotide polymorphism rs1382539, located in a regulatory element of DHFR, was associated with increased levels of short-chain MTX polyglutamates (P = 1.1 x 10(-8)) related to suppression of enhancer activity, whereas rs35789560 in FPGS (p.R466C, P = 5.6 x 10(-9)) was associated with decreased levels of long-chain MTX polyglutamates through reduced catalytic activity. Furthermore, the FPGS variant was linked with increased relapse risk (P = .044). These findings show a genetic basis for interpatient variability in MTX response and could be used to improve future dosing algorithms.
|
|
